1. Field of the Invention
The present invention relates generally to methods for detecting the presence of or risk of developing cancer and more specifically to methods for detecting the presence of hypomethylation of the IGF2 gene.
2. Background Information
The single greatest impediment to cancer diagnosis is the general requirement that the tumor itself must be detected directly. Efforts to identify genetic abnormalities in normal tissues of patients with cancer or at risk of cancer have been disappointing. For example, BRCA1 mutations are present in only about 1% of breast cancers. A small fraction of patients with colorectal cancer have predisposing mutations in the APC gene (>1%), causing adenomatous polyposis coli. An even smaller fraction show mutations in genes responsible for replication error repair (>2% of colon cancer patients, or much less than 1% of the population), show mutations in genes responsible for nucleotide mismatch error repair causing hereditary nonpolyposis colorectal cancer (HNPCC or Lynch syndrome).
Diagnostic methods such as microsatellite instability, require for identification that a patient already have a tumor. For example, microsatellite instability compares microsatellite marker length between the monoclonal tumor cell population and normal tissue derived from the same patient.
Family history still remains the most reliable diagnostic procedure for identifying patients at risk of cancer. A molecular diagnostic approach that might identify patients with cancer or at risk of cancer, using only normal tissue, would offer a decisive advantage for intervention and treatment.
Except for rare hereditary cancer syndromes, the impact of molecular genetics on cancer risk assessment and prevention has been minimal. Cancer surveillance has been effective for some cancers in which risk can be identified, for example colorectal cancer in familial adenomatous polyposis coli and hereditary nonpolyposis colorectal cancer (Markey, L., et al., Curr. Gastroenterol. Rep. 4, 404-413 (2002)), but these syndromes cumulatively account for less than 1% of cancer patients (Samowitz, W. S., et al., Gastroenterology 121, 830-838 (2001); Percesepe, A., et al., J. Clin. Oncol. 19, 3944-3950 (2001)). Nevertheless, genetics is thought to contribute substantially to cancer risk, since the odds ratio for malignancy increases in patients with first degree relatives with cancer, e.g., 2 to 3-fold in colorectal cancer (Fuchs, C. S., et al., N. Engl. J Med. 331, 1669-1674 (1994)). Therefore, there remains a need to develop genetic tests to identify these patients.
Accordingly, no tests are available for identifying common cancer risk in the general population. As discussed above, genetic abnormalities that are known to predispose to cancer are rare. At the same time, advances in cancer treatment have had a small impact on morbidity and mortality. A major advance in cancer requires identification of patients at risk (i.e. identifies patients before they develop cancer), which could be combined with increased surveillance and chemoprevention, similar to the modern approach to cardiovascular medicine.
Thus, there remains a need for a diagnostic method for detecting and/or screening for the presence of diseases and/or the risk of developing a disease. In particular, there remains a need for a method for detecting and/or screening for the presence of cancer, which does not require a tumor sample. There also remains a need for a method of detecting and/or screening for the presence of cancer and/or the risk of developing cancer that can be applied to a wide section of the population.